Resident in adult bone marrow is a cell population called the marrow stromal cells. This pool of pluripotent stem cells is easy to isolate, provides a renewal population and can be used for autologous transplantation. Marrow stromal cells have been shown to differentiate into neuronal cells in the central and peripheral nervous systems in vivo. Little, however, is known about the potential of marrow stromal cells to take on properties of sensory neurons residing in the inner ear structures. The primary goal of this study is to test whether marrow storomal cells can survive, differentiate and establish connectivity within the developing or adult inner ear, and whether signaling proteins secreted from the microenvironment play any instructive roles in these processes. Aim #1 will test whether interactions between marrow stromal cells and tissues surrounding the developing inner ear play an instructive role in tissue-specific neuronal differentiation. Aim #2 will test whether diffusible proteins secreted from the developing inner ear promote migration or axon outgrowth of marrow stromal cells that have been exposed to neural induction signals. Aim #3 will test whether transplanted marrow stromal cells can differentiate and integrate into the inner ear of adult animals or animals with auditory neuropathy. Undifferentiated or partially-differentiated stromal cells will be transplanted into the cochlea of adult normal gerbils or gerbils treated with ouabain. The extent of survival, neuronal differentiation and axon outgrowth of donor stromal cells will be evaluated and compared among different experimental conditions. Together, these experiments would provide critical information on factors essential for the differentiation and integration of bone marrow-derived stem cells in the host cochlear tissue, and thus have significant implications in the development and implementation of an autologous cell replacement therapy in the auditory system. [unreadable] [unreadable]